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Int J Endocrinol. 2012;2012:549081. doi: 10.1155/2012/549081. Epub 2012 Mar 18.

Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling.

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1
Department of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China.

Abstract

OBJECTIVES:

This study aimed to explore the effect of exendin-4 on t-BHP-induced apoptosis in pancreatic β cells and the mechanism of action.

METHODS:

Murine MIN6 pancreatic β cells were treated with exendin-4 in the presence or absence of tert-butyl hydroperoxide (t-BHP). Cell survival was assessed by MTT staining. The percentage of apoptotic cells was determined by fluorescence microscopy analysis after Hoechst/PI staining and flow cytometric assay after Annexin V-FITC/PI staining. The activity of caspase-3 was determined using a caspase-3 activity kit. Expression of P-IRE1α, IRE1α, C-Jun N-terminal kinase (JNK), P-JNK, C-JUN, and P-C-JUN was detected by western blotting.

RESULTS:

Exendin-4 was found to inhibit t-BHP-induced apoptosis in pancreatic β-cells by downregulating caspase-3 activity. Exendin-4 also inhibited the endoplasmic reticulum transmembrane protein IRE1, the apoptosis-related signaling molecule JNK, and c-Jun activation.

CONCLUSIONS:

Our findings suggest that exendin-4 ultimately reduces t-BHP-induced β-cell apoptosis. IRE1-JNK-c-Jun signaling is involved in the exendin-4-mediated modulation of β-cell apoptosis.

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